The long term objective of this grant since its inception has been to improve host defense mechanisms as a means for controlling infections and, thus, reduce morbidity and mortality in surgical patients. After definition of the abnormalities of host defense that occurred during injury and infection, concepts of nutritional pharmacology were used to develop diets using animal models which, in appropriate controlled clinical trials, have resulted in a 20% reduction in hospital stay and a 60 to 70 percent reduction in the incidence of post operative and post traumatic infections. Animal studies of early enteral feeding after traumatic injury also lead to use in severely injured patients with a highly significant reduction in infections in controlled clinical trials. The success of these studies has more narrowly focused recent investigations to the interactions of nutrition, gut function and sepsis. It is now clear that translocation of microbes and their products is a frequent occurrence in both laboratory animals and man. Translocation occurs very rapidly and triggers activation of cytokine, complement and eicosanoid pathways in a regulated and orderly manner resulting in inflammatory processes locally and in distant organs. The magnitude or severity of translocation is associated directly with overall mortality and indirectly with length of survival in animals. Treatments which improve the barrier function to translocation consistently improved survival in injured animals, and conversely, treatment which decreases the gut barrier function increases mortality. Gut barrier function may, therefore, play an important role in a wide variety of diseases. The hypothesis that will be tested ultimately will be that control or prevention of translocation in critically ill patients will improve outcome as measured by a decrease in infectious complications, a decrease in the incidence of the "septic syndrome", a reduction in hospital stay, and, perhaps, an improvement in survival. The specific aims of the present study are: 1) to develop improved tests for the measurement of translocation of microbes and their products, 2) to further delineate the mechanisms whereby microbial translocation occurs, 3) to develop optimal therapeutic regimens for the prevention of translocation, and, 4) to further delineate the pathophysiologic consequences of microbial translocation.